PH26572A - Hypoglycemic thiazolidine-dione derivatives - Google Patents

Hypoglycemic thiazolidine-dione derivatives Download PDF

Info

Publication number: PH26572A
Authority: PH; Philippines
Prior art keywords: methyl; phenyl; compound; oxazolyl; thiazolidine
Prior art date: 1988-03-08

Application number

PH38301A

Other languages

English (en)

Inventor

David Alan Clark

Steven Wayne Goldstein

Bernard Hulin

Original Assignee

Pfizer

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1988-03-08

Filing date

1989-03-08

Publication date

1992-08-19

1989-03-08 Application filed by Pfizer filed Critical Pfizer

1992-08-19 Publication of PH26572A publication Critical patent/PH26572A/en

Links

230000002218 hypoglycaemic effect Effects 0.000 title abstract description 12
150000001467 thiazolidinediones Chemical class 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 61
239000001257 hydrogen Substances 0.000 claims abstract description 23
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 23
239000002253 acid Substances 0.000 claims abstract description 20
150000003839 salts Chemical class 0.000 claims abstract description 20
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 17
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 12
229910052799 carbon Inorganic materials 0.000 claims abstract description 10
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 8
229910052717 sulfur Inorganic materials 0.000 claims abstract description 6
125000002091 cationic group Chemical group 0.000 claims abstract description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
125000001544 thienyl group Chemical group 0.000 claims abstract description 5
125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 4
125000002541 furyl group Chemical group 0.000 claims abstract description 4
125000001624 naphthyl group Chemical group 0.000 claims abstract description 4
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 4
229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
125000001246 bromo group Chemical group Br* 0.000 claims abstract description 3
229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 3
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 3
125000004076 pyridyl group Chemical group 0.000 claims abstract description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 25
210000004369 blood Anatomy 0.000 claims description 14
239000008280 blood Substances 0.000 claims description 14
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 11
239000008103 glucose Substances 0.000 claims description 11
241000124008 Mammalia Species 0.000 claims description 10
125000000217 alkyl group Chemical group 0.000 claims description 7
125000003545 alkoxy group Chemical group 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
229910052727 yttrium Inorganic materials 0.000 claims description 5
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
230000003345 hyperglycaemic effect Effects 0.000 claims description 4
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
230000000260 hypercholesteremic effect Effects 0.000 claims description 3
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 claims description 2
125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims description 2
125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 claims 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 18
150000001473 2,4-thiazolidinediones Chemical class 0.000 abstract description 3
125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 2
125000006274 (C1-C3)alkoxy group Chemical group 0.000 abstract 1
125000006701 (C1-C7) alkyl group Chemical group 0.000 abstract 1
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 100
239000000047 product Substances 0.000 description 94
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 75
-1 cholesteryl ester Chemical class 0.000 description 68
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 55
238000002360 preparation method Methods 0.000 description 47
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
239000000203 mixture Substances 0.000 description 35
ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical class O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 33
229940093499 ethyl acetate Drugs 0.000 description 32
235000019439 ethyl acetate Nutrition 0.000 description 32
238000000034 method Methods 0.000 description 32
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 31
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
239000003921 oil Substances 0.000 description 26
235000019198 oils Nutrition 0.000 description 26
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
239000000243 solution Substances 0.000 description 22
239000012044 organic layer Substances 0.000 description 19
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 18
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 17
239000002904 solvent Substances 0.000 description 17
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 16
238000003756 stirring Methods 0.000 description 16
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
239000003054 catalyst Substances 0.000 description 15
238000001914 filtration Methods 0.000 description 14
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
229940107161 cholesterol Drugs 0.000 description 11
241001465754 Metazoa Species 0.000 description 10
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
150000001299 aldehydes Chemical class 0.000 description 10
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 10
238000010992 reflux Methods 0.000 description 10
239000000741 silica gel Substances 0.000 description 10
229910002027 silica gel Inorganic materials 0.000 description 10
230000000694 effects Effects 0.000 description 9
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
239000012267 brine Substances 0.000 description 8
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 8
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
239000003472 antidiabetic agent Substances 0.000 description 7
239000002585 base Substances 0.000 description 7
239000012043 crude product Substances 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
238000005984 hydrogenation reaction Methods 0.000 description 7
239000000543 intermediate Substances 0.000 description 7
239000007787 solid Substances 0.000 description 7
208000031226 Hyperlipidaemia Diseases 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 6
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical class C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
206010012601 diabetes mellitus Diseases 0.000 description 6
239000003814 drug Substances 0.000 description 6
229940126904 hypoglycaemic agent Drugs 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
150000002632 lipids Chemical class 0.000 description 6
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
239000011734 sodium Substances 0.000 description 6
229910052708 sodium Inorganic materials 0.000 description 6
229910000104 sodium hydride Inorganic materials 0.000 description 6
OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
208000024172 Cardiovascular disease Diseases 0.000 description 5
239000005909 Kieselgur Substances 0.000 description 5
235000012000 cholesterol Nutrition 0.000 description 5
229940079593 drug Drugs 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
239000010410 layer Substances 0.000 description 5
230000009467 reduction Effects 0.000 description 5
159000000000 sodium salts Chemical class 0.000 description 5
239000003981 vehicle Substances 0.000 description 5
201000001320 Atherosclerosis Diseases 0.000 description 4
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
102000004877 Insulin Human genes 0.000 description 4
108090001061 Insulin Proteins 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
150000001336 alkenes Chemical class 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
150000002431 hydrogen Chemical class 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
229940125396 insulin Drugs 0.000 description 4
229910000510 noble metal Inorganic materials 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
125000002971 oxazolyl group Chemical group 0.000 description 4
125000001639 phenylmethylene group Chemical group [H]C(=*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
239000000376 reactant Substances 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
239000012312 sodium hydride Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
238000012360 testing method Methods 0.000 description 4
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
108010007622 LDL Lipoproteins Proteins 0.000 description 3
102000007330 LDL Lipoproteins Human genes 0.000 description 3
241000699670 Mus sp. Species 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
229940123464 Thiazolidinedione Drugs 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
235000005911 diet Nutrition 0.000 description 3
230000037213 diet Effects 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
239000000284 extract Substances 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
MJGFBOZCAJSGQW-UHFFFAOYSA-N mercury sodium Chemical compound [Na].[Hg] MJGFBOZCAJSGQW-UHFFFAOYSA-N 0.000 description 3
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 3
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 3
229910052763 palladium Inorganic materials 0.000 description 3
239000013641 positive control Substances 0.000 description 3
229910001023 sodium amalgam Inorganic materials 0.000 description 3
239000007858 starting material Substances 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
229930192474 thiophene Natural products 0.000 description 3
AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
229910000497 Amalgam Inorganic materials 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
241000551547 Dione <red algae> Species 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 2
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
229940100389 Sulfonylurea Drugs 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
108010069201 VLDL Cholesterol Proteins 0.000 description 2
230000005856 abnormality Effects 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
230000009471 action Effects 0.000 description 2
239000003529 anticholesteremic agent Substances 0.000 description 2
210000000709 aorta Anatomy 0.000 description 2
210000001367 artery Anatomy 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
150000003935 benzaldehydes Chemical class 0.000 description 2
230000037396 body weight Effects 0.000 description 2
244000309464 bull Species 0.000 description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
229960001231 choline Drugs 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
239000006184 cosolvent Substances 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
238000011161 development Methods 0.000 description 2
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
229940043237 diethanolamine Drugs 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
SHZIWNPUGXLXDT-UHFFFAOYSA-N ethyl hexanoate Chemical compound CCCCCC(=O)OCC SHZIWNPUGXLXDT-UHFFFAOYSA-N 0.000 description 2
238000003818 flash chromatography Methods 0.000 description 2
230000010030 glucose lowering effect Effects 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
238000005534 hematocrit Methods 0.000 description 2
125000000623 heterocyclic group Chemical group 0.000 description 2
RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
239000013067 intermediate product Substances 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
230000003902 lesion Effects 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
239000002207 metabolite Substances 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
238000002156 mixing Methods 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
235000019371 penicillin G benzathine Nutrition 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
239000010452 phosphate Substances 0.000 description 2
229960005141 piperazine Drugs 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
239000002243 precursor Substances 0.000 description 2
150000003138 primary alcohols Chemical class 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical class COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
239000002002 slurry Substances 0.000 description 2
210000000329 smooth muscle myocyte Anatomy 0.000 description 2
PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 2
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
230000009466 transformation Effects 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
229960000281 trometamol Drugs 0.000 description 2
208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
238000010792 warming Methods 0.000 description 2
DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 1
BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N 1,1-Diethoxyethane Chemical compound CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
IGBZCOWXSCWSHO-UHFFFAOYSA-N 1-(5-bromothiophen-2-yl)ethanone Chemical compound CC(=O)C1=CC=C(Br)S1 IGBZCOWXSCWSHO-UHFFFAOYSA-N 0.000 description 1
ZHAKAIBZKYHXJS-UHFFFAOYSA-N 2-(chloromethyl)-1,3-thiazole Chemical compound ClCC1=NC=CS1 ZHAKAIBZKYHXJS-UHFFFAOYSA-N 0.000 description 1
FMJHCFNDIDDALR-UHFFFAOYSA-N 2-(chloromethyl)-5-methyl-2-phenyl-3h-1,3-oxazole Chemical compound O1C(C)=CNC1(CCl)C1=CC=CC=C1 FMJHCFNDIDDALR-UHFFFAOYSA-N 0.000 description 1
CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 1
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
FSCWZHGZWWDELK-UHFFFAOYSA-N 3-(3,5-dichlorophenyl)-5-ethenyl-5-methyl-2,4-oxazolidinedione Chemical compound O=C1C(C)(C=C)OC(=O)N1C1=CC(Cl)=CC(Cl)=C1 FSCWZHGZWWDELK-UHFFFAOYSA-N 0.000 description 1
VCTKYTBWZTZPHF-UHFFFAOYSA-N 4-(chloromethyl)-5-methyl-2-phenyl-1,3-oxazole Chemical compound ClCC1=C(C)OC(C=2C=CC=CC=2)=N1 VCTKYTBWZTZPHF-UHFFFAOYSA-N 0.000 description 1
DMWFGRFWJPMKOC-UHFFFAOYSA-N 4-(diethoxymethyl)benzaldehyde;1-[4-(diethoxymethyl)phenyl]ethanol Chemical compound CCOC(OCC)C1=CC=C(C=O)C=C1.CCOC(OCC)C1=CC=C(C(C)O)C=C1 DMWFGRFWJPMKOC-UHFFFAOYSA-N 0.000 description 1
LQJQDHUHMBKCSA-UHFFFAOYSA-N 4-[3-(3,5-dimethyl-2-phenylimidazol-4-yl)propanoyl]benzaldehyde Chemical compound CN1C(CCC(=O)C=2C=CC(C=O)=CC=2)=C(C)N=C1C1=CC=CC=C1 LQJQDHUHMBKCSA-UHFFFAOYSA-N 0.000 description 1
CGKDQGNTTWRPIK-UHFFFAOYSA-N 4-[3-[2-(4-methylphenyl)-1,3-oxazol-4-yl]propanoyl]benzaldehyde Chemical compound C1=CC(C)=CC=C1C1=NC(CCC(=O)C=2C=CC(C=O)=CC=2)=CO1 CGKDQGNTTWRPIK-UHFFFAOYSA-N 0.000 description 1
MIGKRQALZPBTER-UHFFFAOYSA-N 4-[3-[5-methyl-2-(4-methylphenyl)-1,3-oxazol-4-yl]propanoyl]benzaldehyde Chemical compound CC=1OC(C=2C=CC(C)=CC=2)=NC=1CCC(=O)C1=CC=C(C=O)C=C1 MIGKRQALZPBTER-UHFFFAOYSA-N 0.000 description 1
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
BNNMDMGPZUOOOE-UHFFFAOYSA-N 4-methylbenzenesulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1 BNNMDMGPZUOOOE-UHFFFAOYSA-N 0.000 description 1
KNKIXXJBMGWXCY-UHFFFAOYSA-N 5-[(4-acetylphenyl)methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1=CC(C(=O)C)=CC=C1CC1C(=O)NC(=O)S1 KNKIXXJBMGWXCY-UHFFFAOYSA-N 0.000 description 1
XXMDTWIPAQQDDV-UHFFFAOYSA-N 5-[3-(5-methyl-2-phenyl-1,3-oxazol-4-yl)propanoyl]pyridine-2-carbaldehyde Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCC(=O)C1=CC=C(C=O)N=C1 XXMDTWIPAQQDDV-UHFFFAOYSA-N 0.000 description 1
HEFGGAWLJMWCQK-UHFFFAOYSA-N 5-[[4-[1-hydroxy-3-(5-methyl-2-phenyl-1,3-oxazol-4-yl)propyl]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCC(O)C(C=C1)=CC=C1CC1SC(=O)NC1=O HEFGGAWLJMWCQK-UHFFFAOYSA-N 0.000 description 1
RSWAMKPQMAMHFJ-UHFFFAOYSA-N 5-[[4-[3-(3,5-dimethyl-2-phenylimidazol-4-yl)-1-hydroxypropyl]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound CN1C(CCC(O)C=2C=CC(CC3C(NC(=O)S3)=O)=CC=2)=C(C)N=C1C1=CC=CC=C1 RSWAMKPQMAMHFJ-UHFFFAOYSA-N 0.000 description 1
QHTULCIAIDWQKP-UHFFFAOYSA-N 5-[[4-[3-(5-methyl-2-phenyl-1,3-oxazol-4-yl)propyl]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCCC(C=C1)=CC=C1CC1SC(=O)NC1=O QHTULCIAIDWQKP-UHFFFAOYSA-N 0.000 description 1
MGOFABMWSHLJMS-UHFFFAOYSA-N 5-[[4-[3-(furan-2-yl)propanoyl]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound C=1C=C(CC2C(NC(=O)S2)=O)C=CC=1C(=O)CCC1=CC=CO1 MGOFABMWSHLJMS-UHFFFAOYSA-N 0.000 description 1
KAVJVIDWPOYZEG-UHFFFAOYSA-N 5-[[4-[n-hydroxy-c-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethyl]carbonimidoyl]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCC(=NO)C(C=C1)=CC=C1CC1SC(=O)NC1=O KAVJVIDWPOYZEG-UHFFFAOYSA-N 0.000 description 1
WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
208000031104 Arterial Occlusive disease Diseases 0.000 description 1
229940123208 Biguanide Drugs 0.000 description 1
239000004135 Bone phosphate Substances 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
BSMXJTFQKACPSM-UHFFFAOYSA-N CC(C1=NC=C(C=C1)C(CC(=O)OC(C)(C)C)=O)(O[SiH2]C(C)(C)C)C Chemical compound CC(C1=NC=C(C=C1)C(CC(=O)OC(C)(C)C)=O)(O[SiH2]C(C)(C)C)C BSMXJTFQKACPSM-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 1
239000004380 Cholic acid Substances 0.000 description 1
102000008186 Collagen Human genes 0.000 description 1
108010035532 Collagen Proteins 0.000 description 1
206010010071 Coma Diseases 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
102000016942 Elastin Human genes 0.000 description 1
108010014258 Elastin Proteins 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
208000002705 Glucose Intolerance Diseases 0.000 description 1
206010018429 Glucose tolerance impaired Diseases 0.000 description 1
108010023302 HDL Cholesterol Proteins 0.000 description 1
108010010234 HDL Lipoproteins Proteins 0.000 description 1
102000005548 Hexokinase Human genes 0.000 description 1
108700040460 Hexokinases Proteins 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
208000013016 Hypoglycemia Diseases 0.000 description 1
108010028554 LDL Cholesterol Proteins 0.000 description 1
208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 1
208000007101 Muscle Cramp Diseases 0.000 description 1
241001553014 Myrsine salicina Species 0.000 description 1
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
102000016611 Proteoglycans Human genes 0.000 description 1
108010067787 Proteoglycans Proteins 0.000 description 1
125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 1
235000012377 Salvia columbariae var. columbariae Nutrition 0.000 description 1
240000005481 Salvia hispanica Species 0.000 description 1
235000001498 Salvia hispanica Nutrition 0.000 description 1
244000000231 Sesamum indicum Species 0.000 description 1
235000003434 Sesamum indicum Nutrition 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
208000005392 Spasm Diseases 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
208000007536 Thrombosis Diseases 0.000 description 1
JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
229960001466 acetohexamide Drugs 0.000 description 1
VGZSUPCWNCWDAN-UHFFFAOYSA-N acetohexamide Chemical compound C1=CC(C(=O)C)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 VGZSUPCWNCWDAN-UHFFFAOYSA-N 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
230000002411 adverse Effects 0.000 description 1
125000003172 aldehyde group Chemical group 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
229940040526 anhydrous sodium acetate Drugs 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
208000021328 arterial occlusion Diseases 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
230000008901 benefit Effects 0.000 description 1
UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
150000004283 biguanides Chemical class 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
KLJPJQLKSTTYTK-UHFFFAOYSA-N butyl(chloro)silane Chemical compound CCCC[SiH2]Cl KLJPJQLKSTTYTK-UHFFFAOYSA-N 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide Inorganic materials 0.000 description 1
239000002775 capsule Substances 0.000 description 1
RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 1
150000001728 carbonyl compounds Chemical class 0.000 description 1
210000001715 carotid artery Anatomy 0.000 description 1
239000005018 casein Substances 0.000 description 1
BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
235000021240 caseins Nutrition 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
210000001627 cerebral artery Anatomy 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
235000014167 chia Nutrition 0.000 description 1
229960001761 chlorpropamide Drugs 0.000 description 1
BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
235000019416 cholic acid Nutrition 0.000 description 1
229960002471 cholic acid Drugs 0.000 description 1
KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
YZFWTZACSRHJQD-UHFFFAOYSA-N ciglitazone Chemical compound C=1C=C(CC2C(NC(=O)S2)=O)C=CC=1OCC1(C)CCCCC1 YZFWTZACSRHJQD-UHFFFAOYSA-N 0.000 description 1
229950009226 ciglitazone Drugs 0.000 description 1
239000003240 coconut oil Substances 0.000 description 1
235000019864 coconut oil Nutrition 0.000 description 1
229920001436 collagen Polymers 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000002285 corn oil Substances 0.000 description 1
235000005687 corn oil Nutrition 0.000 description 1
210000004351 coronary vessel Anatomy 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
230000018044 dehydration Effects 0.000 description 1
238000006297 dehydration reaction Methods 0.000 description 1
KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
230000000994 depressogenic effect Effects 0.000 description 1
235000021196 dietary intervention Nutrition 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
238000007865 diluting Methods 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 description 1
229960001760 dimethyl sulfoxide Drugs 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
229920002549 elastin Polymers 0.000 description 1
238000010828 elution Methods 0.000 description 1
HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
JOPKBXOEABYGNJ-UHFFFAOYSA-N ethyl 3-[4-(diethoxymethyl)phenyl]-3-oxopropanoate Chemical compound CCOC(OCC)C1=CC=C(C(=O)CC(=O)OCC)C=C1 JOPKBXOEABYGNJ-UHFFFAOYSA-N 0.000 description 1
IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
SLFUXNFVAANERW-UHFFFAOYSA-N ethyl hexanoate;potassium Chemical compound [K].CCCCCC(=O)OCC SLFUXNFVAANERW-UHFFFAOYSA-N 0.000 description 1
229940012017 ethylenediamine Drugs 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
229910052730 francium Inorganic materials 0.000 description 1
239000012458 free base Substances 0.000 description 1
HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 1
AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
238000003304 gavage Methods 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
235000015220 hamburgers Nutrition 0.000 description 1
208000019622 heart disease Diseases 0.000 description 1
ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 1
201000001421 hyperglycemia Diseases 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000000468 ketone group Chemical group 0.000 description 1
231100001231 less toxic Toxicity 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
229910003002 lithium salt Inorganic materials 0.000 description 1
159000000002 lithium salts Chemical class 0.000 description 1
IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical compound [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 description 1
210000002540 macrophage Anatomy 0.000 description 1
VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
239000000347 magnesium hydroxide Substances 0.000 description 1
229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
229960003194 meglumine Drugs 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
GXHMMDRXHUIUMN-UHFFFAOYSA-N methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O GXHMMDRXHUIUMN-UHFFFAOYSA-N 0.000 description 1
AXLHVTKGDPVANO-UHFFFAOYSA-N methyl 2-amino-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound COC(=O)C(N)CNC(=O)OC(C)(C)C AXLHVTKGDPVANO-UHFFFAOYSA-N 0.000 description 1
LXADGPLPPGQZNI-UHFFFAOYSA-N methyl 3-(5-bromothiophen-2-yl)-3-oxopropanoate Chemical compound COC(=O)CC(=O)C1=CC=C(Br)S1 LXADGPLPPGQZNI-UHFFFAOYSA-N 0.000 description 1
229940050176 methyl chloride Drugs 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
125000000896 monocarboxylic acid group Chemical group 0.000 description 1
DCOWODXEBRWFEL-UHFFFAOYSA-N n-benzyl-2-phenylethanamine;n-ethylethanamine Chemical compound CCNCC.C=1C=CC=CC=1CNCCC1=CC=CC=C1 DCOWODXEBRWFEL-UHFFFAOYSA-N 0.000 description 1
230000001338 necrotic effect Effects 0.000 description 1
239000002547 new drug Substances 0.000 description 1
238000010606 normalization Methods 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
239000003538 oral antidiabetic agent Substances 0.000 description 1
229940127209 oral hypoglycaemic agent Drugs 0.000 description 1
125000004304 oxazol-5-yl group Chemical group O1C=NC=C1* 0.000 description 1
COWNFYYYZFRNOY-UHFFFAOYSA-N oxazolidinedione Chemical compound O=C1COC(=O)N1 COWNFYYYZFRNOY-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 1
229960003243 phenformin Drugs 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
229920000166 polytrimethylene carbonate Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
238000012545 processing Methods 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
230000004044 response Effects 0.000 description 1
229910052703 rhodium Inorganic materials 0.000 description 1
239000010948 rhodium Substances 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
150000003333 secondary alcohols Chemical class 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000011775 sodium fluoride Substances 0.000 description 1
235000013024 sodium fluoride Nutrition 0.000 description 1
VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
125000005504 styryl group Chemical group 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
JPAZHDAAXHLULS-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxyperoxy-dimethylsilane Chemical class CC(C)(C)[Si](C)(C)OOO[Si](C)(C)C(C)(C)C JPAZHDAAXHLULS-UHFFFAOYSA-N 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000011285 therapeutic regimen Methods 0.000 description 1
OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
229960002277 tolazamide Drugs 0.000 description 1
229960005371 tolbutamide Drugs 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
229910052720 vanadium Inorganic materials 0.000 description 1
239000011782 vitamin Substances 0.000 description 1
229940088594 vitamin Drugs 0.000 description 1
229930003231 vitamin Natural products 0.000 description 1
235000013343 vitamin Nutrition 0.000 description 1
150000003722 vitamin derivatives Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/34—Oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Diabetes (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Hematology (AREA)
Veterinary Medicine (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Obesity (AREA)
Endocrinology (AREA)
Emergency Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Thiazole And Isothizaole Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Medicines Containing Plant Substances (AREA)
Separation Using Semi-Permeable Membranes (AREA)
Photoreceptors In Electrophotography (AREA)
Paints Or Removers (AREA)
Indole Compounds (AREA)
Hydrogenated Pyridines (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

PH38301A 1988-03-08 1989-03-08 Hypoglycemic thiazolidine-dione derivatives PH26572A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
PCT/US1988/000733 WO1989008651A1 (en)	1988-03-08	1988-03-08	Hypoglycemic thiazolidinedione derivatives

Publications (1)

Publication Number	Publication Date
PH26572A true PH26572A (en)	1992-08-19

Family

ID=22208589

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
PH38301A PH26572A (en)	1988-03-08	1989-03-08	Hypoglycemic thiazolidine-dione derivatives

Country Status (25)

Country	Link
EP (1)	EP0332332B1 (de)
JP (1)	JP2610990B2 (de)
KR (1)	KR910000723B1 (de)
AT (1)	ATE87624T1 (de)
AU (1)	AU593754B2 (de)
CA (1)	CA1328873C (de)
CZ (1)	CZ285957B6 (de)
DD (1)	DD279245A5 (de)
DE (1)	DE68905639T2 (de)
DK (1)	DK108089A (de)
EG (1)	EG19168A (de)
ES (1)	ES2053977T3 (de)
FI (1)	FI93115C (de)
IE (1)	IE62776B1 (de)
IL (1)	IL89482A (de)
MX (1)	MX15171A (de)
MY (1)	MY103979A (de)
NO (1)	NO177008C (de)
NZ (1)	NZ228249A (de)
PH (1)	PH26572A (de)
PL (1)	PL159728B1 (de)
PT (1)	PT89912B (de)
WO (1)	WO1989008651A1 (de)
YU (1)	YU47066B (de)
ZA (1)	ZA891680B (de)

Families Citing this family (59)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5089514A (en) *	1990-06-14	1992-02-18	Pfizer Inc.	3-coxazolyl [phenyl, chromanyl or benzofuranyl]-2-hydroxypropionic acid derivatives and analogs as hypoglycemic agents
FI930772L (fi) *	1990-08-23	1993-02-22	Pfizer	Hydroxiureaderivat som saenker glugosnivao i blodet
GB9023585D0 (en) *	1990-10-30	1990-12-12	Beecham Group Plc	Novel compounds
TW222626B (de) *	1991-07-22	1994-04-21	Pfizer
US5175179A (en) *	1991-09-25	1992-12-29	Pfizer Inc.	Method for treating hypertension
FR2696743B1 (fr) *	1992-10-12	1994-12-23	Adir	Nouveaux composés de thiazolidine dione, leur procédé de préparation et les compositions pharmaceutiques les contenant.
TW245716B (de) *	1992-12-28	1995-04-21	Takeda Pharm Industry Co
US5614544A (en) *	1993-09-14	1997-03-25	Takeda Chemical Industries, Ltd.	Oxazolidinedione derivatives and their use
US6046222A (en) *	1993-09-15	2000-04-04	Warner-Lambert Company	Use of thiazolidinedione derivatives in the treatment of polycystic ovary syndrome, gestational diabetes and disease states at risk for progressing to noninsulin-dependent diabetes mellitus
US5457109A (en) *	1993-09-15	1995-10-10	Warner-Lambert Company	Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of disease states at risk for progressing to noninsulin-dependent diabetes mellitus
CN1103590C (zh) *	1993-09-15	2003-03-26	三共株式会社	使用噻唑烷二酮防止或延缓非胰岛素依赖性糖尿病(niddm)的发作
US5874454A (en) *	1993-09-15	1999-02-23	Warner-Lambert Company	Use of thiazolidinedione derivatives in the treatment of polycystic ovary syndrome, gestational diabetes and disease states at risk for progressing to noninsulin-dependent diabetes mellitus
IL113112A (en) *	1994-03-28	2000-06-01	Nissan Chemical Ind Ltd	Pyridine substituted thiazolidinediones and pharmaceutical compositions comprising them
WO1996005186A1 (en) *	1994-08-10	1996-02-22	Takeda Chemical Industries, Ltd.	Thiazolidinedione derivatives, their production and use
US5925656A (en) *	1995-04-10	1999-07-20	Dr. Reddy's Research Foundation	Compounds having antidiabetic, hypolipidemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them
US5708012A (en) *	1995-04-28	1998-01-13	Sankyo Company, Limited	Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of insulin resistant subjects with normal glucose tolerance in order to prevent or delay the onset of noninsulin-dependent mellitus
NZ286920A (en) *	1995-07-03	1997-06-24	Sankyo Co	Use of combination of hmg-coa reductase inhibitors and of insulin sensitizers for the prevention/treatment of arteriosclerosis or xanthoma
NZ314406A (en) *	1996-03-18	2000-12-22	Sankyo Co	Treatment or prophylaxis of pancreatitis with a medicament containing an insulin sensitiser including oxazoles and thiazoles
ZA973850B (en) *	1996-05-06	1997-12-02	Reddy Research Foundation	Novel antidiabetic compounds having hypolipidaemic, anti-hypertensive properties, process for their preparation and pharmaceutical compositions containing them.
US5801173A (en) *	1996-05-06	1998-09-01	Dr. Reddy's Research Foundation	Heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them
US5919782A (en) *	1996-05-06	1999-07-06	Dr. Reddy's Research Foundation	Heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them
ZA973848B (en) *	1996-05-06	1997-12-02	Reddy Research Foundation	Novel heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them.
CA2257284C (en) *	1996-05-31	2005-10-04	Sankyo Company Limited	Remedy for autoimmune diseases
AU744518B2 (en)	1996-07-01	2002-02-28	Dr. Reddy's Laboratories Limited	Novel heterocyclic compounds process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases
US6114526A (en) *	1996-07-01	2000-09-05	Dr. Reddy's Research Foundation	Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases
US6372750B2 (en)	1996-07-01	2002-04-16	Dr. Reddy's Research Foundation	Heterocyclic compounds, process for their preparation and pharmaceutical compounds containing them and their use in the treatment of diabetes and related diseases
US5885997A (en) *	1996-07-01	1999-03-23	Dr. Reddy's Research Foundation	Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases
USRE39266E1 (en) *	1996-07-01	2006-09-05	Dr. Reddy's Laboratories, Limited	Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases
HU225415B1 (en)	1996-07-15	2006-11-28	Sankyo Co	Medicinal compositions comprising cs-866 and insulin resistance improving agents and their use for the treatment of arteriosclerosis and xanthoma
JP2000514041A (ja) *	1996-07-26	2000-10-24	ドクター・レディーズ・リサーチ・ファウンデーション	抗糖尿病、低脂血、抗高血圧特性を有するチアゾリジンジオン化合物、それらの調製法、及びその薬学的組成物
JP2001514663A (ja)	1997-03-12	2001-09-11	エスモンド，ロバートダブリュー．	アルツハイマー病を処置または予防するための方法
DE19711616A1 (de)	1997-03-20	1998-09-24	Boehringer Mannheim Gmbh	Verbessertes Verfahren zur Herstellung von Thiazolidindionen
EP1671637A3 (de)	1997-06-18	2007-12-19	SmithKline Beecham P.L.C.	Behandlung der Diabetes mit Thiazolidindione und Sulphonylurea
GB9715295D0 (en) *	1997-07-18	1997-09-24	Smithkline Beecham Plc	Novel method of treatment
GB9715306D0 (en) *	1997-07-18	1997-09-24	Smithkline Beecham Plc	Novel method of treatment
HUP9902721A2 (hu)	1997-11-25	1999-12-28	The Procter & Gamble Co.	Tömény textillágyító készítmény és ehhez alkalmazható magas telítetlenségű textillágyító vegyület
AU1507799A (en) *	1997-12-16	1999-07-05	Sankyo Company Limited	Leukemia remedy
GB9824893D0 (en) *	1998-11-12	1999-01-06	Smithkline Beckman Corp	Novel method of treatment
DZ2937A1 (fr)	1998-11-12	2004-03-15	Smithkline Beecham Plc	Compositions nouvelles de sensibilidants à l'insuline.
WO2000028989A1 (en) *	1998-11-12	2000-05-25	Smithkline Beecham P.L.C.	Pharmaceutical composition for modified release of an insulin sensitiser and another antidiabetic agent
US6191154B1 (en)	1998-11-27	2001-02-20	Case Western Reserve University	Compositions and methods for the treatment of Alzheimer's disease, central nervous system injury, and inflammatory diseases
ID29875A (id) *	1999-07-01	2001-10-18	Geron Corp Cs	Penghambat-penghambat telomerase dan metode penggunaannya
JP2001072592A (ja)	1999-07-01	2001-03-21	Kyowa Hakko Kogyo Co Ltd	テロメラーゼ阻害剤
CO5200844A1 (es)	1999-09-17	2002-09-27	Novartis Ag	Una combinacion que comprende nateglinida y cuando por menos otro compuesto antidiabetico usada para el tratamiento de desordenes metabolicos, especialmente diabetes, o de una enfermedad o condicion asociada con dibetes
US6878749B2 (en)	1999-09-17	2005-04-12	Novartis Ag	Method of treating metabolic disorders, especially diabetes, or a disease or condition associated with diabetes
US6559188B1 (en)	1999-09-17	2003-05-06	Novartis Ag	Method of treating metabolic disorders especially diabetes, or a disease or condition associated with diabetes
ATE385421T1 (de)	2000-01-21	2008-02-15	Novartis Pharma Gmbh	Zusammensetzungen bestehend aus dipeptidylpeptidase-iv inhibitoren und antidiabetica
JP2001199888A (ja) *	2000-01-24	2001-07-24	Fujimoto Brothers:Kk	糖尿病治療剤
US6680387B2 (en)	2000-04-24	2004-01-20	Aryx Therapeutics	Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis
GB0014969D0 (en)	2000-06-19	2000-08-09	Smithkline Beecham Plc	Novel method of treatment
AU2001294673A1 (en)	2000-09-21	2002-04-02	Aryx Therapeutics	Isoxazolidine compounds useful in the treatment of diabetes, hyperlipidemia, andatherosclerosis
US6452014B1 (en)	2000-12-22	2002-09-17	Geron Corporation	Telomerase inhibitors and methods of their use
US7659409B2 (en)	2002-03-19	2010-02-09	Mitsubishi Chemical Corporation	3-Hydroxy-3-(2-thienyl) propionamides and production method thereof, and production method of 3-amino-1-(2-thienyl)-1-propanols using the same
US8268352B2 (en)	2002-08-05	2012-09-18	Torrent Pharmaceuticals Limited	Modified release composition for highly soluble drugs
US8216609B2 (en)	2002-08-05	2012-07-10	Torrent Pharmaceuticals Limited	Modified release composition of highly soluble drugs
TWI330639B (en) *	2005-11-15	2010-09-21	Otsuka Pharma Co Ltd	Oxazole compound and pharmaceutical composition
US20120094959A1 (en)	2010-10-19	2012-04-19	Bonnie Blazer-Yost	Treatment of cystic diseases
EP2914250B1 (de)	2012-11-05	2018-04-04	Commissariat à l'Énergie Atomique et aux Énergies Alternatives	Kombination aus einem antikrebsmittel wie einem tyrosinekinaseinhibitor und einem stat5-antagonisten, vorzugsweise einem thiazolidindion, zur entfernung von hämatologischen krebsstammzellen in vivo und zur verhinderung eines blutkrebsrezidivs
WO2016071727A1 (en)	2014-11-04	2016-05-12	INSERM (Institut National de la Santé et de la Recherche Médicale)	Methods for the prevention and the treatment of rapidly progressive glomerulonephritis

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS5522636A (en) *	1978-08-04	1980-02-18	Takeda Chem Ind Ltd	Thiazoliding derivative
CN1003445B (zh) *	1984-10-03	1989-03-01	武田药品工业株式会社	噻唑烷二酮衍生物，其制备方法和用途
WO1986007056A1 (en) *	1985-05-21	1986-12-04	Pfizer Inc.	Hypoglycemic thiazolidinediones
FI904414A7 (fi) *	1988-03-08	1990-09-07	Pfizer	Tiatsolidiinidioni-hypoglykeemisesti vaikuttavat aineet
WO1989008652A1 (en) *	1988-03-08	1989-09-21	Pfizer Inc.	Thiazolidinedione derivatives as hypoglycemic agents

1988
- 1988-03-08 WO PCT/US1988/000733 patent/WO1989008651A1/en not_active Ceased
- 1988-03-08 MX MX1517189A patent/MX15171A/es unknown
1989
- 1989-03-01 EP EP89302017A patent/EP0332332B1/de not_active Expired - Lifetime
- 1989-03-01 AT AT89302017T patent/ATE87624T1/de not_active IP Right Cessation
- 1989-03-01 DE DE8989302017T patent/DE68905639T2/de not_active Expired - Fee Related
- 1989-03-01 ES ES89302017T patent/ES2053977T3/es not_active Expired - Lifetime
- 1989-03-03 IL IL89482A patent/IL89482A/xx not_active IP Right Cessation
- 1989-03-06 CA CA000592855A patent/CA1328873C/en not_active Expired - Fee Related
- 1989-03-06 EG EG11789A patent/EG19168A/xx active
- 1989-03-06 PT PT89912A patent/PT89912B/pt not_active IP Right Cessation
- 1989-03-06 ZA ZA891680A patent/ZA891680B/xx unknown
- 1989-03-06 MY MYPI89000271A patent/MY103979A/en unknown
- 1989-03-07 CZ CS891439A patent/CZ285957B6/cs not_active IP Right Cessation
- 1989-03-07 IE IE73889A patent/IE62776B1/en not_active IP Right Cessation
- 1989-03-07 PL PL1989278115A patent/PL159728B1/pl unknown
- 1989-03-07 DD DD89326340A patent/DD279245A5/de not_active IP Right Cessation
- 1989-03-07 KR KR1019890002787A patent/KR910000723B1/ko not_active Expired
- 1989-03-07 AU AU31078/89A patent/AU593754B2/en not_active Ceased
- 1989-03-07 DK DK108089A patent/DK108089A/da not_active Application Discontinuation
- 1989-03-07 NZ NZ228249A patent/NZ228249A/xx unknown
- 1989-03-07 YU YU47989A patent/YU47066B/sh unknown
- 1989-03-08 PH PH38301A patent/PH26572A/en unknown
- 1989-03-08 JP JP1055968A patent/JP2610990B2/ja not_active Expired - Fee Related
- 1989-11-06 FI FI895258A patent/FI93115C/fi not_active IP Right Cessation
- 1989-11-07 NO NO894425A patent/NO177008C/no not_active IP Right Cessation

Also Published As

Publication number	Publication date
DE68905639D1 (de)	1993-05-06
ES2053977T3 (es)	1994-08-01
FI93115B (fi)	1994-11-15
PT89912B (pt)	1994-05-31
MY103979A (en)	1993-10-30
PL278115A1 (en)	1989-10-30
DE68905639T2 (de)	1993-07-08
IE890738L (en)	1989-09-08
DK108089D0 (da)	1989-03-07
JPH01272574A (ja)	1989-10-31
NZ228249A (en)	1990-05-28
IL89482A0 (en)	1989-09-10
IL89482A (en)	1993-04-04
FI93115C (fi)	1995-02-27
YU47989A (en)	1990-12-31
CA1328873C (en)	1994-04-26
ATE87624T1 (de)	1993-04-15
EP0332332A1 (de)	1989-09-13
PT89912A (pt)	1989-11-10
EP0332332B1 (de)	1993-03-31
YU47066B (sh)	1994-12-28
KR890014533A (ko)	1989-10-24
KR910000723B1 (ko)	1991-01-31
MX15171A (es)	1993-05-01
CZ143989A3 (cs)	1999-06-16
ZA891680B (en)	1990-10-31
CZ285957B6 (cs)	1999-12-15
FI895258A0 (fi)	1989-11-06
NO177008B (no)	1995-03-27
AU3107889A (en)	1989-09-14
IE62776B1 (en)	1995-02-22
NO894425L (no)	1989-11-07
AU593754B2 (en)	1990-02-15
EG19168A (en)	1995-02-28
DK108089A (da)	1989-10-27
WO1989008651A1 (en)	1989-09-21
JP2610990B2 (ja)	1997-05-14
PL159728B1 (en)	1993-01-29
NO894425D0 (no)	1989-11-07
NO177008C (no)	1995-07-05
DD279245A5 (de)	1990-05-30

Publication	Publication Date	Title
EP0332332B1 (de)	1993-03-31	Hypoglykämische Thiazolidindion-Derivate
US5036079A (en)	1991-07-30	Hypoglycemic thiazolidinedione derivatives
US5330998A (en)	1994-07-19	Thiazolidinedione derivatives as hypoglycemic agents
CA2029703C (en)	1996-10-15	Oxazolidinedione hypoglycemic agents
EP0332331B1 (de)	1994-02-09	Hypoglykämische Thiazolidindion-Derivate
EP0389699B1 (de)	1994-05-11	Thiazolidin-Derivate als hypoglykämisches Mittel
EP0544696B1 (de)	1995-01-11	Hypoglykämische hydroxyharnstoffderivate
US5037842A (en)	1991-08-06	Oxa- and thiazolidinedione hypoglycemic and hypocholesterolemic agents
US5223522A (en)	1993-06-29	Thiazolidinedione hypoglycemic agents
US5130379A (en)	1992-07-14	Hypoglycemic thiazolidinedione derivatives
US5498621A (en)	1996-03-12	Oxazolidinedione hypoglycemic agents
EP0319189A1 (de)	1989-06-07	Thiazolidindione als hypoglykämische und antiatherosklerotische Mittel
CZ12494A3 (en)	1994-07-13	Hypoglycaemic thiazolidinediones, process of their preparation, use and intermediates of such process
EP0591252B1 (de)	1996-09-11	Thiazolidindione als hypoglykämische wirkstoffe
WO1991003474A1 (en)	1991-03-21	Hypoglycemic thiazolidinedione derivatives
IE63187B1 (en)	1995-03-22	Thiazolidinedione derivatives as hypoglycemic agents
HU204820B (en)	1992-02-28	Process for producing thiazolidinedione derivatives and pharmaceutical compositions comprising such compounds